Using C-11 labelled N-Methyl spiperone as a dopamine (DA) D2 receptor ligand, we propose to examine patients with bipolar major affective disorder longitudinally with PET scans. Patients will be scanned in the euthymic, hypo-manic and depressed states. When possible, patients will be rescanned and compared to themselves in different phases of the illness. They will also be compared to other patients in the same phase of illness, including a majority of drug-free patients, and normal controls, to assess changes in central dopaminergic mechanisms associated with the phases of the disease, and their relationship to psychopathological, pharmacological, biochemical, psychological and structural brain findings on CT. This may aid in subtyping the illness, and amplify understanding of the etiology and treatment of affective disorder. The role of the DA system in affective disorder has been raised, but remains unresolved. The use of the PET to image the D2 receptor in vivo will provide further useful information to support or weaken this assertion.